Healthy
Conditions
Keywords
Bioequivalence, Subjects
Brief summary
The objective of this study was to evaluate the comparative bioavailability between Mycophenolate Mofetil 500 mg Tablets (test) and CellCept® 500 mg tablets (reference), after a single-dose in healthy subjects under fasting conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
DRUGCellCept® Tablets
CellCept® Tablets, 500 mg
DRUGMycophenolate Mofetil
Mycophenolate Mofetil Tablet 500 mg
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy, non-smoking male subjects, 18 years of age or older. * Healthy, non-smoking post-menopausal or surgically sterile females 18 years of age or older. * BMI ≥ 19 and ≤ 30. * Negative for: 1. HIV. 2. Hepatitis B surface antigen and Hepatitis C antibody. 3. Using drugs of abuse test (marijuana, amphetamines, barbiturates, cocaine, opiates, benzodiazepines and methadone). 4. Urine cotinine test 5. Serum HCG consistent with pregnancy (females only) * No significant diseases or clinically significant findings in a physical examination. * No clinically significant abnormal laboratory values. * No clinically significant findings in vital signs measurements and a 12-lead electrocardiogram (ECG). * Be informed of the nature of the study and given written consent prior to receiving any study procedure. * Females who participate in this study must be unable to have children: 1. post-menopausal for at least 1 year - no menstrual cycle for 12 months and LH and FSH levels judged by a physician to be consistent with post-menopausal status. OR 2. Proof of surgical sterility. * Females who participate in this study are not pregnant and/or non-lactating.
Exclusion criteria
* Known history or presence of any clinically significant medical condition. * Known or suspected carcinoma. * Known or suspected increased susceptibility to infection. * Known history or presence of active tuberculosis (TB). * Results of a previous TB skin test greater than 5 mm in diameter. * Lived in or traveled, during the last 8 weeks, to a country defined by the Public Health Agency of Canada as having WHO estimated sputum smear positive pulmonary TB rate of 15 per 100,000 or higher. * Known history or presence of: 1. Hypersensitivity or idiosyncratic reaction to mycophenolate mofetil and/or any other drug substances with similar activity. 2. Alcoholism within the last 12 months. 3. Drug dependence and/or substance abuse. 4. Use of tobacco or nicotine-containing products within the last 6 months. * On a special diet within 4 weeks prior to drug administration (e.g. liquid, protein, raw food diet). * Participated in another clinical trial or received and investigational product within 30 days prior to drug administration. * Donated up to 250 mL of blood within the previous 30 days OR Donated from 251 to 499 mL of blood in the previous 45 days OR Donated more than 499 mL of blood in the previous 56 days (based on the Canadian Blood Services guideline for blood donation. * Females taking oral or transdermal hormonal contraceptives within 14 days preceding period 1 dosing. * Females having taken implanted or injected hormonal contraceptives within 6 months prior to period 1 dosing. * Requirement of any non-topical medication (prescription and/or over-the-counter) on a routine basis. * Difficulty fasting or consuming the standard meals. * Do not tolerate venipuncture. * Unable to read or sign the ICF.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Observed Concentration | Blood samples collected over 72 hour period | Bioequivalence based on Cmax |
| AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | Blood samples collected over 72 hour period | Bioequivalence based on AUC0-inf |
| AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | Blood samples collected over 72 hour period | Bioequivalence based on AUC0-t |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mycophenolate Mofetil (Test) First Mycophenolate Mofetil Tablets, 500 mg dosed in first period followed by CellCept® Tablets, 500 mg dosed in second period; sequence repeated in third and fourth periods. | 20 |
| Cellcept® (Reference) First CellCept® Tablets, 500 mg dosed in first period followed by Mycophenolate Mofetil Tablets, 500 mg dosed in second period; sequence repeated in third and fourth periods. | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Mycophenolate Mofetil (Test) First | Cellcept® (Reference) First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 20 Participants | 40 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Black | 5 Participants | 8 Participants | 13 Participants |
| Race/Ethnicity, Customized Caucasian | 12 Participants | 12 Participants | 24 Participants |
| Region of Enrollment Canada | 20 participants | 20 participants | 40 participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 20 Participants | 18 Participants | 38 Participants |
Outcome results
Primary
AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)
Bioequivalence based on AUC0-inf
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study was included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mycophenolate Mofetil | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 26.6752 µg*hr/mL | Standard Deviation 6.7137 |
| Cellcept® | AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | 26.7354 µg*hr/mL | Standard Deviation 7.1533 |
90% CI: [98.74, 105.39]
Primary
AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)
Bioequivalence based on AUC0-t
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study was included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mycophenolate Mofetil | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 25.2539 µg*hr/mL | Standard Deviation 6.6843 |
| Cellcept® | AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) | 25.3253 µg*hr/mL | Standard Deviation 6.8009 |
90% CI: [95.99, 103.98]
Primary
Cmax - Maximum Observed Concentration
Bioequivalence based on Cmax
Time frame: Blood samples collected over 72 hour period
Population: Data from all subjects who completed the study was included in the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mycophenolate Mofetil | Cmax - Maximum Observed Concentration | 11.0939 µg/mL | Standard Deviation 6.3067 |
| Cellcept® | Cmax - Maximum Observed Concentration | 11.1715 µg/mL | Standard Deviation 4.7689 |
90% CI: [80.25, 110.04]